This invention relates to the chemical neutralization of pressure-sensitive adhesive polymers or copolymers containing acrylic acid or methacrylic acid incorporated in their polymer chains.
Polymers based on acrylic acid or methacrylic acid and on esters thereof are of particular importance among pressure-sensitive adhesives since they are not only backbone builders and are frequently the main component of a pressure-sensitive adhesive formulation, but also possess pressure-sensitive adhesive qualities themselves. This constitutes a fundamental difference to mixtures of natural or synthetic rubbers (backbone builders) with natural or synthetic resins (so-called tackifiers), for example. With polyacrylate-based pressure-sensitive adhesives there is no necessity of adding low-molecular components in order to provide them with pressure-sensitive adhesive properties. Besides the manifold possibilities for technical application, the latter quality renders the pressure-sensitive polyacrylate adhesives particularly attractive for medicinal use in humans or animals. Low-molecular componentsxe2x80x94mostly resins, as required as tackifying additives to rubbersxe2x80x94can cause irritation and even allergic reactions when absorbed via the skin. This risk is for the most part non-existent in polyacrylates, which is why these are also described as xe2x80x9chypoallergenicxe2x80x9d in medicinal use.
Pressure-sensitive polyacrylate adhesives are today widely used in the production of medicinal patches for wound treatment or fixation in medicinal operations (key word xe2x80x9cadhesive patchxe2x80x9d). Furthermore they represent the most significant group of pressure-sensitive adhesives used for making transdermal therapeutic systems (TTSs).
Apart from their good skin compatibility, the reasons therefor lie in the following properties:
Polyacrylates can be composed in manifold ways from a large selection of monomers. In this way, it is possible to adjust the pressure-sensitive adhesive properties of the polymers and their affinity to the surfaces which are to be bonded, e.g. human skin, within broad limits. In this connection, it is, in particular, the chemical nature of the lateral chains on the polyacrylate backbone which plays a crucial part. The lateral chains not only determine hydrophilia-lipophilia balance within the polymer, and thus, for example, the amount of moisture that can be absorbed: by means of appropriate lateral chains and the mixture thereof it is, in particular, possible to reduce the crystallinity of the polymer. A reduction of the crystallinity and thereby of the glass transition temperature has a positive effect on the pressure-sensitive adhesive properties of the polymer by promoting the flowability and thereby the quick wetting of the surfaces. For medicinal applications of TTSs a low glass transition temperature is of particular importance: In the non-crystalline state, the polymer, that is, its side chains are particularly permeable to pharmaceutic active substances and auxiliaries contained. This is essential for the quick release at the site of application.
Polyacrylates possess a high solubility for most pharmaceutic active substances. Typically, it is higher than in other pressure-sensitive adhesives suitable for the production of TTSs such as, for instance, natural rubber-resin mixtures, or in pressure-sensitive silicone adhesives. Frequently, the required quantities of an active substance can actually be dissolvedxe2x80x94and thereby incorporated in a TTS in the form most suitable for deliveryxe2x80x94in polyacrylates only. When polymerising unesterified acrylic or methacrylic acid in polyacrylates, the latter can carry free carboxyl groups on their chain. These carboxyl groups are suitable for later connecting several polymer chains with each other via the groups. Typical reagents which are generally known to those skilled in the art are organometallic complexes such as, for example, aluminium or titanyl acetyl acetonate. These introduce polyvalent cations into the polymer, which cations then simultaneously bind to several carboxyl groups on different polymer chains. In this way, it is possible to crosslink linear polymer chains three-dimensionally. Typically, this takes place when heating and drying the corresponding polymer solution in the course of processing to yield the final product. Other possibilities of crosslinking result from irradiation of high-energy quanta of light, e.g. UV radiation, in combination with suitable crosslinking reagents. Crosslinking prevents the flowability of the polymer mass while maintaining a deformability which has remained essentially elastic only. When crosslinking is dispensed with, typically there occurs an unwanted slow flowxe2x80x94known as xe2x80x9ccold flowxe2x80x9dxe2x80x94of the pressure-sensitive adhesive under action of any outer force, in the most simple case: gravity. Upon application on the skin, cold flow can lead to the pressure-sensitive adhesive penetrating the pores of the skin more deeply than wanted, and thereby make removal more difficult, and thus painful. Here, too, the capacity for crosslinking affords corresponding advantages. It is thus one of the most important qualities of polyacrylates.
Polyacrylates are obtained from polymerisation of the vinyl residue of acrylic or methacrylic acid. This mechanism enables in a very simple manner the incorporation of foreign monomers (non-(meth)acrylates), which likewise contain an ethylenically unsaturated molecule part. These are, for example, ethylene, vinyl acetate or other esters of vinyl alcohol, and especially various vinyl pyrrolidones, as well as styrene and crotamiton. In the field of medicinal pressure-sensitive adhesives one finds, for example, numerous mixed polymers with vinylpyrrolidones. These enable the adjustment of higher solubilities of certain active substances, or also of higher moisture absorption or moisture tolerance on the skin as application site.
Altogether, not only in the field of technical applications do polyacrylates represent an indispensable group of pressure-sensitive adhesives. In particular in medicinal application, polyacrylates are of outstanding importance due to the sum of their positive properties in combination with their being available at low cost.
The present invention relates to the chemical modification of acid polyacrylate pressure-sensitive adhesives. The term acid polyacrylate pressure-sensitive adhesives means polymers possessing the following properties:
the polymer has pressure-sensitive adhesive properties at room temperature
relative to the mean polymer mass, at least 50% (w/w) thereof are monomers from the group of acrylic or methacrylic acid or ester derivatives thereof
relative to the mean polymer mass, 0.5% (w/w), but at maximum 10% (w/w) thereof, are unesterified acrylic or methacrylic acids.